Pharm - Drugs For Depressive Disorders

Selegiline is a selective inhibitor of MAO B.

Learning objective: describe the main contraindication of tricyclic antidepressants.
Answer: A
Tricyclic antidepressants (especially amitriptyline) have pronounced anticholinergic properties
and are therefore contraindicated in open angle glaucoma (since they can hinder the outflow of
the aqueous humor) and in cardiac arrhythmias (since they can increase AV conduction).
B, C, D, E, F) These drugs do not have anticholinergic activity.

Learning objective: describe the serotonin syndrome due SSRIs/SNRIs
Answer: C
The history, the symptoms and signs of the patient indicate that she was most likely suffering
from a serotonin syndrome. The disorder is a rare but potentially fatal interaction that can be
caused by several drugs either alone or in combination, when given in high doses. These
include antidepressants, opioids, psychostimulants, triptans, psychedelics, herbs (St. John’s
wort, ginseng, nutmeg). The combination of two drugs that enhance serotonin transmission (i.e.
SSRIs/SNRIs with MAO inhibitors or with tricyclics antidepressants) can be particularly
dangerous. The syndrome involves mental, autonomic and neurological disorders of sudden
onset less than 24 hours after the beginning of treatment or an overdose.
For mild cases the discontinuation of the offending drug is the only needed treatment..
For more serious cases th therapy includes benzodiazepines for agitation and somatic effects,
serotonin antagonists (cyproheptadine) or atypical neuroleptics with serotonin blocking activity
(like olanzapine), beta-blockers for tachycardia and autonomic instability, and dantrolene for
hyperthermia.
A, B, D, E, F) These disorders do not cause the signs and symptoms reported by the patient.

The correct answer is C. Patients that overdose on tricyclic medications experience dangerous and often lethal arrhythmias. These arrhythmias may produce hypotension, shock, and death. Thus, monitoring for the cardiac consequences of these drugs is paramount in treating tricyclic overdoses. Tricyclics can lead to the development of QT prolongation, cardiac arrhythmias, AV block, and bundle-branch block. Tricyclics act by directly blocking the fast Na channels in cardiac myocytes. The antimuscarinic side effects can result in cardiotoxicity, convulsions, and coma. Supportive management may include treatment with IV sodium bicarbonate, which can treat ventricular arrhythmias that are associated with tricyclic antidepressants. Sodium bicarbonate acts by alkalinizing the serum to oppose the arrhythmia induced by the tricyclics and by directly providing Na for the fast channels. Because tricyclics can potentially cause fatal arrythmias in potentially suicidal patients, they have largely been supplanted by newer agents such as the SSRls. When tricyclics are prescribed, they are often prescribed in smaller amounts than the typical prescription.

Aspiration of gastric contents (choice A) is infrequent in tricyclic overdose. It is a more common cause of death in patients that overdose on sedative-hypnotics or narcotics.

Direct hepatotoxicity (choice B) is not produced in tricyclic overdose. Acetaminophen and mushroom ingestion produce hepatic failure and death.

Renal toxicity (choice D) is not a common cause of death in tricyclic overdose.
Respiratory depression (choice E) is a common cause of death in sedative-hypnotic and narcotic overdoses. Other causes of death from these types of ingestion include coma and aspiration of gastric contents_

Learning objective: explain the mechanism of paroxetine induced diarrhea
Answer: B
By blocking serotonin reuptake, SSRIs like paroxetine increase 5-HT availability at serotonergic
synapses both in the central and in the enteric nervous system. Serotonin activation of 5-HT
receptors (mainly 5HT-2A) is known to increase intestinal peristalsis so causing diarrhea.
A, C, D, E, F) Paroxetine does not cause these actions. Moreover all these action would lead to
constipation, not diarrhea.

Learning objective: describe the main adverse effects of SSRIs/SNRIs
Answer: B
Abrupt discontinuation of an SSRI or SNRI can cause a variety of symptoms that can be quite
distressing. These include dizziness, nausea and vomiting, flulike symptoms, irritability and
anxiety. Symptoms usually emerge one to three days after the last dose. Paroxetine and
sertraline are most likely to cause the discontinuation syndrome, and they should be tapered
over several weeks.
A, C, D, E) These disorders do not cause the symptoms reported by the patient.

Learning objective: explain the mechanism of action of SNRIs
Answer: C
Venlafaxine is today a first choice agent for anxiety disorders. The drug blocks both
norepinephrine and serotonin transporters so inhibiting the reuptake of these neurotransmitters,
which in turn increases their availability into the synaptic cleft of CNS neurons.
A) Tricyclic antidepressant like amitriptyline also block monoamine transporters but they are not
used as antianxiety agents.
B) Citalopram blocks the serotonin transporter but not the norepinephrine transporter.
D) Benzodiazepines do not alter monoamine reuptake.
E, F) These drugs block only norepinephrine transporter (bupropion) or serotonin transporter
(trazodone) and are not used as antianxiety agents.

Learning objective: describe the main adverse effects of SSRIs/SNRIs
Answer: C
Most antidepressants can cause sexual dysfunction, but its incidence seems the highest with
SSRIs/SNRIs (mainly paroxetine and fluoxetine) and the lowest with bupropion and mirtazapine.
Sexual dysfunction seems mainly related to the increased activity of the central serotonergic
system, since serotonin is mainly an inhibitory neurotransmitter in the CNS.
B) Tricyclic antidepressant can frequently cause sexual dysfunction but the are contraindicated
in this patient because they can cause cardiac arrhythmias in patient at risk (patient with a
previous episode of ventricular arrhythmia have a very high risk of a recurrent arrhythmia).
D) this drugs is not used for depressive disorder and can cause arrhythmias in patient at risk.
A, B, F) These drugs rarely cause sexual dysfunction.

Amitriptyline is the correct answer because it can prolong the Q-T interval on an ECG.

Amitriptyline is the correct answer because it has pronounced anticholinergic properties. Anticholinergic properties refer to the ability of a drug to block the neurotransmitter acetylcholine, leading to various effects such as dry mouth, blurred vision, constipation, and urinary retention. Amitriptyline is a tricyclic antidepressant that exhibits strong anticholinergic effects, making it useful for treating conditions such as depression, anxiety, and chronic pain.

Learning objective: describe the adverse effect of tricyclic antidepressants.
Answer: C
All tricyclic antidepressants block alpha-1 adrenergic receptors and therefore can cause
postural hypotension, especially during the first week of treatment. Autonomic effects usually
undergo tolerance, at least partially, so the symptom tends to diminish over time.
A, B, D, E, F) These drugs caused very rarely postural hypotension.

Learning objective: describe the main adverse effects of SSRIs/SNRIs.
Answer: B
Most antidepressants can cause sexual dysfunction, but its incidence seems the highest with
SSRIs/SNRIs. Symptoms of sexual dysfunction include erectile dysfunction, priapism, delayed
ejaculation, decreased vaginal lubrication and clitoral congestion, decreased libido, partial or
complete anorgasmia.
A, C, D, E, F) SNRIs do not cause these symptoms.

Learning objective: describe the use of paroxetine in social anxiety disorder.
Answer: E
The patient was most likely suffering from a social anxiety disorder (SAD). Several trials have
provided evidence of efficacy of pharmacotherapy with SSRIs or SNRIs in social anxiety
disorder. Approximately one-fifth of patient with SAD also suffer from an alcohol use disorder,
like in the present case. Paroxetine significantly reduced social anxiety and decreased the
frequency of alcohol use in patients with both disorders.
A) Benzodiazepines should be reserved as the last line agents in patient with SAD.
B, C, D, F) These drugs are not effective in SAD.

Learning objective: describe the main adverse effects of SSRIs/SNRIs
Answer: E
SSRIs/SNRIs are generally considered activating compounds and they can cause sleep
disturbances in up to 30%of patient. Fluoxetine is widely regarded as the most activating of
SSRIs, a property that my be desirable in anergic patients or undesirable in those who are
agitated or suffer from insomnia.
A) Lorazepam is used as an antianxiety agent but tend to cause sleep, not insomnia.
A, B, C, F) These drugs are used rarely, or not at all, in generalized anxiety disorder.

Learning objective: explain the mechanism of action of amitriptyline.
Answer: A
Tricyclic antidepressants are potent inhibitors of norepinephrine and serotonin reuptake into
presynaptic terminals, and therefore increase monoamine availability in the synaptic cleft of
central neurons. The only other drug class that can act by the same mechanism are SNRIs (like
venlafaxine and duloxetine). The choice of a tricyclic antidepressant in this case is appropriate
since these drugs are also sometime used to treat migraine, a disorder frequently associate to
depression, like in the present case.
B, C, D, E ,F) (see explanation above)

Bupropion is the correct answer because it is known to increase the availability of norepinephrine in the synaptic cleft. It does not have a significant effect on serotonin (5-HT) levels.

Learning objective: describe the therapeutic uses of mirtazapine.
Answer: B
When an SSRIs drug is not effective, switching to another SSRI or to a non SSRI
antidepressant is appropriate. Mirtazapine is an antidepressant with sedative properties and
therefore is suitable for an agitated patient, like in the present case.
A, C, D,) These drugs are not used in depressive disorders.
E) Bupropion is an antidepressant used to increase the effect of another antidepressant
(augmentation therapy) or to substitute another antidepressant. However it is not indicated in
this case since bupropion has excitatory effects and the patient is agitate and restless.

Learning objective: describe the main drug interactions with SSRIs
Answer: D
The symptoms of the patient indicate that he is suffering from an extrapyramidal adverse effect.
SSRIs are inhibitors of the p450 enzymes and can increase the activity of other drugs given
concomitantly. Specifically paroxetine is a potent inhibitor of the CYP2D6 isozyme which is the
main isozyme that metabolizes metoclopramide. Therefore the dopamine blocking actions of
metoclopramide are enhanced, leading to extrapyramidal effects. Moreover SSRIs can indirectly
affect dopaminergic transmission. In fact serotonin and dopamine appear to have an inverse
relationship in certain areas of the brain, whereby central stimulation of 5-HT receptors result in
inhibition of dopaminergic transmission. The SSRIs-metoclopramide interaction is well know
and occurs rapidly, within hours of metoclopramide administration, like in the present case.
A, B, C, E, F) These interaction of these drugs with metoclopramide is negligible.

Learning objective: Explain the most likely mechanism underlying the therapeutic
effectiveness of most antidepressant drugs.
Answer: C
Tricyclic antidepressants inhibit monoamine reuptake into presynaptic terminals, MAO inhibitors
inhibit monoamine metabolisms, SSRIS inhibit serotonin reuptake into presynaptic terminals. In
all cases there is an increase availability of monoamines in the synaptic cleft which in turn
causes a down regulation of postsynaptic CNS receptors (mainly beta-adrenergic and
serotonergic). This could explain why most antidepressant drugs exert their molecular effects in
a matter of hours whereas their antidepressant effect is delayed of several days, and seems to
indicate that down-regulation is the necessary event for antidepressant efficacy. These findings
have suggested the dysregulation hypothesis of depression: the illness would be the result
of a dysregulated neurotransmitter system and antidepressants would repair or reset the
equilibrium in the system.
A) MAO inhibitors, but not other antidepressants, inhibit monoamine metabolism
B, D, E) (see explanation above)

Learning objective: describe the poisoning with tricyclic antidepressants.
Answer: F
The symptoms of tricyclic overdose are related to their pronounced anticholinergic and alpha
blocking properties. Mydriasis, dry mouth, constipation and urinary retention are common.
A, B, C, D, E) Tricyclic antidepressant tend to cause symptoms opposite to those listed.

Fluoxetine is the correct answer because it has an active metabolite with a half-life of about 10 days. This means that even after the drug is no longer being taken, the metabolite remains in the body and continues to have an effect.